The present invention provides novel proteins, along with therapeutic, diagnostic and research utilities for these proteins.
Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lymphokines, interferons, CSFs and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques clone novel polynucleotides xe2x80x9cdirectlyxe2x80x9d in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent xe2x80x9cindirectxe2x80x9d cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader sequence motif, as well as various PCR-based or low stringency hybridization cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity by virtue of their secreted nature in the case of leader sequence cloning, or by virtue of the cell or tissue source in the case of PCR-based techniques. It is to these proteins that the present invention is directed.
In one embodiment, the present invention provides a composition comprising an isolated protein encoded by a polynucleotide selected from the group consisting of:
(a) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:1;
(b) a polynucleotide comprising the nucleotide sequence of SEQ ID NO:1 from nucleotide 14 to nucleotide 400;
(c) a polynucleotide comprising the nucleotide sequence of the full-length protein coding sequence of clone AM931 deposited under accession number ATCC 98026;
(d) a polynucleotide encoding the full-length protein encoded by the cDNA insert of clone AM931 deposited under accession number ATCC 98026;
(e) a polynucleotide comprising the nucleotide sequence of the mature protein coding sequence of clone AM931 deposited under accession number ATCC 98026;
(f) a polynucleotide encoding the mature protein encoded by the cDNA insert of clone AM931 deposited under accession number ATCC 98026;
(g) a polynucleotide encoding a protein comprising the amino acid sequence of SEQ ID NO:2;
(h) a polynucleotide encoding a protein comprising a fragment of the amino acid sequence of SEQ ID NO:2 having biological activity;
(i) a polynucleotide which is an allelic variant of a polynucleotide of (a)-(f) above; and
(j) a polynucleotide which encodes a species homologue of the protein of (g) or (h) above.
Preferably, such polynucleotide comprises the nucleotide sequence of SEQ ID NO:1 from nucleotide 14 to nucleotide 400; the nucleotide sequence of the full-length protein coding sequence of clone AM931 deposited under accession number ATCC 98026; or the nucleotide sequence of the mature protein coding sequence of clone AM931 deposited under accession number ATCC 98026. In other preferred embodiments, the polynucleotide encodes the full-length or mature protein encoded by the cDNA insert of clone AM931 deposited under accession number ATCC 98026. In yet other preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:2 from amino acid 1 to amino acid 120. In further preferred embodiments, such polynucleotide encodes a protein comprising the amino acid sequence of SEQ ID NO:2 from amino acid 86 to amino acid 128.
In other embodiments, the present invention provides a composition comprising a protein, wherein said protein comprises an amino acid sequence selected from the group consisting of:
(a) the amino acid sequence of SEQ ID NO:2;
(b) the amino acid sequence of SEQ ID NO:2 from amino acid 1 to amino acid 120;
(c) the amino acid sequence of SEQ ID NO:2 from amino acid 86 to amino acid 128;
(d) fragments of the amino acid sequence of SEQ ID NO:2; and
(e) the amino acid sequence encoded by the cDNA insert of clone AM931 deposited under accession number ATCC 98026;
the protein being substantially free from other mammalian proteins. Preferably such protein comprises the amino acid sequence of SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:2 from amino acid 1 to amino acid 120, or the amino acid sequence of SEQ ID NO:2 from amino acid 86 to amino acid 128.
Protein compositions of the present invention may further comprise a pharmaceutically acceptable carrier. Compositions comprising an antibody which specifically reacts with such protein are also provided by the present invention.
Methods are also provided for preventing, treating or ameliorating a medical condition which comprises administering to a mammalian subject a therapeutically effective amount of a composition comprising a protein of the present invention and a pharmaceutically acceptable carrier. Preferably such methods comprise treating a subject to produce an effect selected from the group consisting of inhibition of angiogenesis, inhibition of growth or proliferation of vascular endothelial cells, inhibition of tumor growth and inhibition of angiogenesis-dependent tissue growth.